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letrozole success

letrozole success

What is Femara - Letrozole?

Femara (generic name is letrozole) is an oral drug which can be an effective fertility treatment for women with ovulation problems, or for those with unexplained infertility.

This medication is in a class of drug called aromatase inhibitors. Femara has mainly been used to treat certain cases of breast cancer.

How to Use Femara

Femara is offered in 2.5-milligram yellow, film-coated tablet. Based on when your period begins, your doctor will advise you when to start treatment. Treatment will be taken over five consecutive days.

Some fertility experts recommend taking the pills on days 3, 4, 5, 6 and 7 of your cycle. Others endorse days 5, 6, 7, 8, and 9. While there remains debate on which option is truly best, current research seems to suggest that success rates are more-or-less the same.

Based on when treatment began, you can anticipate when you would need to start having sex:

If you started treatment on day 3, you likely ovulate sometime between day 14 and day 17 of your cycle. To conceive, you would want to begin having sex before you ovulate. In this scenario, you would begin having sex every day (or every other day) starting on day 11 and ending on day 18.

If you started treatment on day 5, you would most likely ovulate between days 16 and 19. In this case, would start having sex between days 13 and 21.

To better pinpoint the time of ovulation, you can use an ovulation predictor kit. You would start testing once you've completed treatment and test daily until you receive a positive result (indicating that you are nearing ovulation). This is the signal to begin having sex.

Femara can also be used for intrauterine insemination (IUI) treatment. Clomid is sometimes prescribed alongside Femara and taken together on the same days.

How do aromatase inhibitors work?

Estrogens are produced by the conversion of androgens through the activity of the enzyme aromatase. Estradiol (E2, the relevant estrogen) produced by the ovary in turn, exerts a negative feedback effect (inhibits) on follicle stimulating hormone (FSH) release from the hypothalamic-pituitary axis (in the brain).

When Letrozole blocks aromatase activity, there is a drop in E2 levels and release of the hypothalamic/pituitary axis from estrogenic negative feedback. The resultant increase in FSH secretion stimulates growth of ovarian follicles.

Because AIs do not deplete estrogen receptors, as does clomiphene citrate, normal central feedback mechanisms remain intact. As the dominant follicle grows and estrogen levels rise, normal negative feedback occurs centrally, resulting in suppression of FSH and atresia of the smaller growing follicles. A single dominant follicle, and mono-ovulation, should occur in most cases.

With aromatase inhibition, there is a temporary increase in androgen levels in the ovary. Androgens are known to increase the sensitivity of the follicles to FSH.

What about twins? Triplets?

The risk of twins with letrozole is estimated to be approximately 3-5%, which appears to be lower than the risk of twins with clomiphene citrate (7-8%), but is still higher than the risk of twins in a spontaneous pregnancy (2-3%).   Although triplets and higher-order pregnancies are rare, these may occur <1% of the time.

What are the side effects?

The most commonly reported side effects of short-term use include fatigue or dizziness, which occur in approximately 10-20% of patients.

Is the risk of birth defects increased?

Letrozole may increase the risk of birth defects if taken when pregnant. Therefore, all patients need a blood draw to check B-hCG and progesterone levels prior to starting the medication.

The use of letrozole prior to pregnancy (as utilized for ovulation induction) has also been studied to evaluate the risk of birth defects.

One study compared the incidence of birth defects in 911 newborns of women conceived following letrozole or clomiphene citrate did not find a difference between the two groups. The rate of birth defects in the study was 2.5-5%, consistent with the national rate of birth defects for all women trying to conceive with or without infertility. (Tulandi, Fertility and Sterility, 2006).

In the NIH trial described earlier, the rate of birth defects was not significantly different between letrozole and clomiphene citrate patients (4.9% of 102 infants, and 1.5% of 66 infants, respectively). (Legro et al, New England Journal of Medicine, 2014).

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